Cargando…

Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort

Prenatal exposure to lead (Pb) is known to decrease fetal growth; but its effects on postnatal growth and mechanistic insights linking Pb to growth are not clearly defined. Genomically imprinted genes are powerful regulators of growth and energy utilization, and may be particularly vulnerable to env...

Descripción completa

Detalles Bibliográficos
Autores principales: Nye, Monica D., King, Katherine E., Darrah, Thomas H., Maguire, Rachel, Jima, Dereje D., Huang, Zhiqing, Mendez, Michelle A., Fry, Rebecca C., Jirtle, Randy L., Murphy, Susan K., Hoyo, Cathrine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258134/
https://www.ncbi.nlm.nih.gov/pubmed/28123784
http://dx.doi.org/10.1093/eep/dvv009
_version_ 1782498992086581248
author Nye, Monica D.
King, Katherine E.
Darrah, Thomas H.
Maguire, Rachel
Jima, Dereje D.
Huang, Zhiqing
Mendez, Michelle A.
Fry, Rebecca C.
Jirtle, Randy L.
Murphy, Susan K.
Hoyo, Cathrine
author_facet Nye, Monica D.
King, Katherine E.
Darrah, Thomas H.
Maguire, Rachel
Jima, Dereje D.
Huang, Zhiqing
Mendez, Michelle A.
Fry, Rebecca C.
Jirtle, Randy L.
Murphy, Susan K.
Hoyo, Cathrine
author_sort Nye, Monica D.
collection PubMed
description Prenatal exposure to lead (Pb) is known to decrease fetal growth; but its effects on postnatal growth and mechanistic insights linking Pb to growth are not clearly defined. Genomically imprinted genes are powerful regulators of growth and energy utilization, and may be particularly vulnerable to environmental Pb exposure. Because imprinting is established early and maintained via DNA methylation, we hypothesized that prenatal Pb exposure alters DNA methylation of imprinted genes resulting in lower birth weight and rapid growth. Pb was measured by inductively coupled plasma mass spectrometry (ICP-MS) in peripheral blood of 321 women of the Newborn Epigenetic STudy (NEST) obtained at gestation ∼12 weeks. Linear and logistic regression models were used to evaluate associations between maternal Pb levels, methylation of differentially methylated regions (DMRs) regulating H19, MEG3 , PEG3 , and PLAGL1 , measured by pyrosequencing, birth weight, and weight-for-height z score gains between birth and age 1 year, ages 1–2 years, and 2–3 years. Children born to women with Pb levels in the upper tertile had higher methylation of the regulatory region of the MEG3 DMR imprinted domain (β = 1.57, SE = 0.82, P  = 0.06). Pb levels were also associated with lower birth weight (β = −0.41, SE = 0.15, P  = 0.01) and rapid gains in adiposity (OR = 12.32, 95% CI = 1.25–121.30, P  = 0.03) by age 2–3 years. These data provide early human evidence for Pb associations with hypermethylation at the MEG3 DMR regulatory region and rapid adiposity gain – a risk factor for childhood obesity and cardiometabolic diseases in adulthood.
format Online
Article
Text
id pubmed-5258134
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-52581342017-01-23 Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort Nye, Monica D. King, Katherine E. Darrah, Thomas H. Maguire, Rachel Jima, Dereje D. Huang, Zhiqing Mendez, Michelle A. Fry, Rebecca C. Jirtle, Randy L. Murphy, Susan K. Hoyo, Cathrine Environ Epigenet Research Article Prenatal exposure to lead (Pb) is known to decrease fetal growth; but its effects on postnatal growth and mechanistic insights linking Pb to growth are not clearly defined. Genomically imprinted genes are powerful regulators of growth and energy utilization, and may be particularly vulnerable to environmental Pb exposure. Because imprinting is established early and maintained via DNA methylation, we hypothesized that prenatal Pb exposure alters DNA methylation of imprinted genes resulting in lower birth weight and rapid growth. Pb was measured by inductively coupled plasma mass spectrometry (ICP-MS) in peripheral blood of 321 women of the Newborn Epigenetic STudy (NEST) obtained at gestation ∼12 weeks. Linear and logistic regression models were used to evaluate associations between maternal Pb levels, methylation of differentially methylated regions (DMRs) regulating H19, MEG3 , PEG3 , and PLAGL1 , measured by pyrosequencing, birth weight, and weight-for-height z score gains between birth and age 1 year, ages 1–2 years, and 2–3 years. Children born to women with Pb levels in the upper tertile had higher methylation of the regulatory region of the MEG3 DMR imprinted domain (β = 1.57, SE = 0.82, P  = 0.06). Pb levels were also associated with lower birth weight (β = −0.41, SE = 0.15, P  = 0.01) and rapid gains in adiposity (OR = 12.32, 95% CI = 1.25–121.30, P  = 0.03) by age 2–3 years. These data provide early human evidence for Pb associations with hypermethylation at the MEG3 DMR regulatory region and rapid adiposity gain – a risk factor for childhood obesity and cardiometabolic diseases in adulthood. Oxford University Press 2016-02-15 /pmc/articles/PMC5258134/ /pubmed/28123784 http://dx.doi.org/10.1093/eep/dvv009 Text en © The Author 2016. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Nye, Monica D.
King, Katherine E.
Darrah, Thomas H.
Maguire, Rachel
Jima, Dereje D.
Huang, Zhiqing
Mendez, Michelle A.
Fry, Rebecca C.
Jirtle, Randy L.
Murphy, Susan K.
Hoyo, Cathrine
Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title_full Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title_fullStr Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title_full_unstemmed Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title_short Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort
title_sort maternal blood lead concentrations, dna methylation of meg3 dmr regulating the dlk1/meg3 imprinted domain and early growth in a multiethnic cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258134/
https://www.ncbi.nlm.nih.gov/pubmed/28123784
http://dx.doi.org/10.1093/eep/dvv009
work_keys_str_mv AT nyemonicad maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT kingkatherinee maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT darrahthomash maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT maguirerachel maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT jimaderejed maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT huangzhiqing maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT mendezmichellea maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT fryrebeccac maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT jirtlerandyl maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT murphysusank maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort
AT hoyocathrine maternalbloodleadconcentrationsdnamethylationofmeg3dmrregulatingthedlk1meg3imprinteddomainandearlygrowthinamultiethniccohort